Immunologic and physiologic parameters of isolated pancreatic islet transplantation will be investigated in several directions. First, the mechanism of islet allograft rejection will be elucidated by determining the relative roles of cell-mediated vs. humorally-mediated factors in immunologic destruction of islet grafts. In conjunction, several methods directed at either altering islet immunogenicity or host immune mechanisms will be studied in an attempt to prolong islet allograft survival. Whole organ pancreatic allografts will also be compared to isolated islets with regard to the ability of these various regimens to prolong survival. Second, islets in intrasplenic and intraportal (intrahepatic) implantation sites will be compared with regard to: 1) differences in islet allograft survival in each site using standardized immunosuppressive protocols; 2) physiologic differences in the function of islets and their ability to maintain normal glucose homeostasis in each site; and 3) their effects on the inappropriate hyperglucagonemia of experimental diabetes. All of the foregoing will be performed using the inbred rat models. Third, short term preservation requirements for pancreatic fragment grafts will be studied using a large animal model (dog). Using various media and culture techniques, an attempt will be made to extend survival of these grafts ex vivo to 48-72 hours followed by successful function after transplantation. Metabolic studies will be performed on recipients of these preserved grafts.